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Differential roles of factors IX and XI in murine placenta and hemostasis under conditions of low tissue factor.

ABSTRACT: The intrinsic tenase complex (FIXa-FVIIIa) of the intrinsic coagulation pathway and, to a lesser extent, thrombin-mediated activation of FXI, are necessary to amplify tissue factor (TF)-FVIIa-initiated thrombin generation. In this study, we determined the contribution of murine FIX and FXI to TF-dependent thrombin generation in vitro. We further investigated TF-dependent FIX activation in mice and the contribution of this pathway to hemostasis. Thrombin generation was decreased in FIX- but not in FXI-deficient mouse plasma. Furthermore, injection of TF increased levels of FIXa-antithrombin complexes in both wild-type and FXI-/- mice. Genetic studies were used to determine the effect of complete deficiencies of either FIX or FXI on the survival of mice expressing low levels of TF. Low-TF;FIX-/y male mice were born at the expected frequency, but none survived to wean. In contrast, low-TF;FXI-/- mice were generated at the expected frequency at wean and had a 6-month survival equivalent to that of low-TF mice. Surprisingly, a deficiency of FXI, but not FIX, exacerbated the size of blood pools in low-TF placentas and led to acute hemorrhage and death of some pregnant dams. Our data indicate that FIX, but not FXI, is essential for survival of low-TF mice after birth. This finding suggests that TF-FVIIa-mediated activation of FIX plays a critical role in murine hemostasis. In contrast, FXI deficiency, but not FIX deficiency, exacerbated blood pooling in low-TF placentas, indicating a tissue-specific requirement for FXI in the murine placenta under conditions of low TF.

SUBMITTER: Grover SP

PROVIDER: S-EPMC6960463 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Differential roles of factors IX and XI in murine placenta and hemostasis under conditions of low tissue factor.

Grover Steven P SP Schmedes Clare M CM Auriemma Alyson C AC Butler Emily E Parrish Molly L ML Miszta Adam A Cleuren Audrey C AC Visser Mayken M Heitmeier Stefan S Posma Jens J JJ Spronk Henri M HM Antoniak Silvio S Wolberg Alisa S AS Pawlinski Rafal R Gailani David D Mackman Nigel N

Blood advances 20200101 1

The intrinsic tenase complex (FIXa-FVIIIa) of the intrinsic coagulation pathway and, to a lesser extent, thrombin-mediated activation of FXI, are necessary to amplify tissue factor (TF)-FVIIa-initiated thrombin generation. In this study, we determined the contribution of murine FIX and FXI to TF-dependent thrombin generation in vitro. We further investigated TF-dependent FIX activation in mice and the contribution of this pathway to hemostasis. Thrombin generation was decreased in FIX- but not i ...[more]

PMID: 31935292

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Dataset Information

Differential roles of factors IX and XI in murine placenta and hemostasis under conditions of low tissue factor.

Publications

Differential roles of factors IX and XI in murine placenta and hemostasis under conditions of low tissue factor.

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